San Diego, CA - Risk factors for large-vessel peripheral arterial disease (LV-PAD) differ from those for small-vessel PAD (SV-PAD), suggesting a different pathophysiology for the two conditions, a new study shows.

Dr Victor Aboyans (Dupuytren University Hospital, Limoges, France) and colleagues report their results online May 30, 2006 in Circulation [1]. They found that current smoking, ratio of total to HDL cholesterol, lipoprotein (a), and high-sensitive CRP were related to LV-PAD progression, whereas only diabetes was associated with SV-PAD progression.

The findings point to the importance of thinking about small- and large-vessel PAD separately and should be a reminder to doctors to look for both when assessing blood flow in the legs, the researchers stress.

Aboyans—who conducted the study while a visiting scholar at the University of California, San Diego—and colleagues examined 403 men and women with LV-PAD and 290 with SV-PAD who were previously suspected of having PAD and underwent evaluation. For the current analysis, results from these initial examinations were compared with new tests performed an average of 4.6 years later.

They measured ankle-brachial index (ABI) and toe-brachial index (TBI) during follow up—most patients showed a significant deterioration in ABI and TBI, although some remained stable. Those suffering the steepest declines (the highest 10%), with at least a 0.30 decrease in ABI or 0.27 decrease in TBI, were considered to have major PAD progression. They compared risk factors in these patients with those who did not have major PAD progression.

"Among traditional risk factors, current smoking appeared to be the most powerful predictor of LV-PAD progression," say Aboyans et al, adding that "smoking cessation is considered a first-line treatment among smokers with PAD." Those with a high ratio of total cholesterol to HDL were also more likely to have their PAD substantially progress.

And although heavy drinking (more than 21 drinks per week) was associated with worse LV-PAD, this was considered "borderline predictive" of PAD progression, as was higher pulse pressure.

The scientists also analyzed several novel cardiovascular risk factors and found that high levels of Lp(a) and high levels of CRP were predictive of greater progression of LV-PAD. However, high levels of homocysteine, previously identified as a risk factor for PAD, did not predict progression.

"To the best of our knowledge, this is the first study with an objective quantification reporting the role of Lp(a) in PAD progression," they comment.

In an American Heart Association press statement, Aboyans says: "The most surprising result was the absence of an impact of diabetes in large-vessel PAD progression."

Conversely, for SV-PAD, the only significant predictor of progression was diabetes (HR 2.65; p=0.042). "Our data show the unique role of diabetes in the progression of this condition in an approximately five-year follow-up."

The researchers note that they did not find any correlation between CRP and SV-PAD progression, "which conflicts with the Rotterdam Study findings in the brain." However, "it should be emphasized that the number of subjects included in the SV-PAD progression analysis was lower than those included in the LV-PAD progression analysis," they point out.

Overall, the results indicate how important it is to consider SV-PAD and LV-PAD independently, they say.

"Some patients in the study had progressive artery blockage, but the only initial evidence was in the toes," says coauthor Dr Michael Criqui (University of California, San Diego). "Particularly in patients with diabetes, doctors may need to measure both ABI and TBI."

The findings reinforce new ACC/AHA guidelines on the management of PAD, published in Circulation in March [2], the researchers add. These recommend antiplatelet therapy and statin treatment.

"If you have PAD and are taking low-dose aspirin and a statin, you're doing two very helpful things," Criqui concludes.